Project 411568

Polycystic ovary syndrome (PCOS) is the most common cause of female infertility in the world. Around 10% of pre-menopausal women are affected with PCOS, making it the most common endocrine disorder in this population. Symptoms of PCOS include, but are not limited to, hirsutism (excessive body hair), acne, ovarian cysts, and infertility. While several therapies are now available, they only alleviate the symptoms, and a significant proportion of women do not respond to these treatments nor tolerate their side effects. As such, it is critical to understand the causes at the root of this syndrome. Several culprits have been identified, one of which is the hypothalamus. The hypothalamus is an area of the brain that acts as an integrative hub, controlling every aspect of endocrinology. In PCOS, this interface is thought to be over-activated, leading to the symptoms observed in patients. It is well established that this neuroendocrine centre is exquisitely sensitive to sex steroid hormones (androgens, progestagens, estrogens). It has been indicated that inappropriate exposure to such steroids, namely androgens, during fetal life may be a factor leading to PCOS. The main objective of our research is to understand how the circuits in the hypothalamus become hyperactive following androgen exposure. We hypothesize that a population of neuronal cells, called GABA neurons, fail to function normally, leading to excessive excitatory outputs to the cells in the hypothalamus that regulate reproductive function, generating female infertility. We aim to use novel transgenic neuroscience techniques (opto-genetics and chemo-genetics) to investigate whether specific inhibition of these neurons in a preclinical model of PCOS can determine whether or not these neurons could be targeted as an effective treatment avenue for PCOS.